The crossed intestines surgery in parabiotic rats produces large changes in daily food intake and energy expenditure that appear to be sustained for the rest of the animal's lives. One rat in each pair can eat three to four times as much as its partner. A major objective of this grant proposal is to determine how these large changes in daily food intake will affect gastric distension, gastric emptying and intestinal transit in order to understand the role of the gastrointestinal tract in the control of daily intake. These experiments will determine which sections of the gastrointestinal tract are stimulated by the food eaten by these rats throughout the 17 hour feeding period. Another objective is to extend pilot studies that show that there are also large changes in oxygen consumption and sympathetic nervous system activity in crossed intestines rats. The possible mechanisms for the changes in overall energy expenditure will be assessed by measuring the rate of norepinephrine turnover, the stimulation of hepatic mRNA levels by thyroid hormones and the amount of uncoupling protein in brown adipose tissue. The final objective is to determine how these large changes in food intake and energy expenditure could be caused by changes in the plasma levels of various hormones and metabolites. The major plasma nutrients, glucose, lactate, glycerol, triglycerides and free fatty acids, will be measured in these rats at several times during the 17 hour feeding period and the plasma level of three pancreatic hormones, insulin, glucagon and somatostatin, will be determined. The long-term objective of this research is to find a medical treatment (drug or hormone analog) for obesity. In Western societies, obesity is a major medical problem that causes a great deal of human suffering. It is associated with such chronic and debilitating conditions as diabetes, hypertension, stroke and heart disease. An effective medical treatment for obesity would improve the quality of life for millions of people and would greatly reduce the cost of long-term health care.